Enhanced efficacy antiperspirant compositions containing strontium

ABSTRACT

The present invention relates to enhanced efficacy antiperspirant salts containing strontium and an amino acid or a hydroxy acid and particularly to stabilized aqueous solutions of such salts. The present invention also embraces methods of making these antiperspirant salts and solutions and compositions containing same.

BACKGROUND OF THE INVENTION

The present invention relates to enhanced efficacy antiperspirantcompositions containing strontium. It also relates to enhanced efficacyantiperspirant salts containing strontium and an amino acid or a hydroxyacid and particularly to stabilized aqueous solutions of such salts. Thepresent invention additionally embraces methods of making theseantiperspirant salts and solutions and compositions containing same.

Enhanced efficacy aluminum and aluminum-zirconium antiperspirant saltsare well known and are described, for example, in GB 2,048,229 and U.S.Pat. No. 4,775,528. These salts are generally made by heat treating arelatively dilute solution of the salt (e.g., about 10% by weight) toincrease its HPLC peak 4 to peak 3 ratio, then spray drying to a powder.These salts typically have an HPLC peak 4 to peak 3 area ratio of 0.7 orhigher, with at least 70% of the aluminum contained in said peaks.However, these enhanced salts are also known to rapidly revert back totheir non-enhanced state (for example, as evidenced by an HPLC peak 4 topeak 3 area ratio of 0.3 or less) in aqueous solution, particularly atconcentrations greater than 20%. Consequently, the enhancedantiperspirant salts are generally only available in powder form and,thus, are generally only formulated into finished formulations assuspended powders in order to retain their enhanced efficacy.

In U.S. Pat. No. 6,042,816, there are described enhanced efficacyantiperspirant salts that are stable in aqueous solution. These saltsinclude a soluble calcium salt such as calcium chloride and a solubleamino acid such as glycine. Typically, these salts have a Ca:Al+Zrweight ratio of about 1:1 to about 1:28 and an amino acid:Al+Zr weightratio of about 2:1 to about 1:20. Because these salts retain theirenhanced efficacy in aqueous solution, they have an advantage overconventional enhanced efficacy salts that revert to the non-enhancedform in aqueous solution.

In U.S. Pat. No. 5,804,203, there a re described topical compositionsthat contain an irritant ingredient (e.g., organic alcohol, carboxylicacid, keto acid, peroxide, etc.), an anti-irritant divalent strontiumcation, and a cosmetic or therapeutic active ingredient. The strontiumcation is said to reduce skin irritation that would otherwise resultfrom the irritant ingredient. Example 11 illustrates an antiperspirantcomposition that includes aluminum chlorohydrate, ethanol and strontiumnitrate. This composition does not include an amino acid or a zirconiumsalt.

In U.S. Pat. No. 5,788,956, it is suggested that perspiration can becontrolled by topically applying a substance P antagonist. Varioussubstance P antagonists are disclosed including peptide and non-peptidenitrogenous derivatives and salts of monovalent, divalent and trivalentcations. The latter includes strontium, magnesium, cobalt, nickel,manganese, barium, etc. Examples 1, 3 and 4 of the patent disclosecompositions containing strontium chloride or strontium nitrate.However, the patent does not provide any sweat reduction data for theexemplified compositions. In contrast to the suggestion in this patent,it has been found that a clear gel product containing 5% strontiumnitrate does not provide any measurable sweat reduction.

It would be highly desirable to provide enhanced efficacy antiperspirantcompositions with superior efficacy, and particularly to provideenhanced efficacy antiperspirant salts which are stable in aqueoussolution. This would make it possible to use the enhanced salts infinished formulations that require a soluble salt form, such as thecurrently attractive clear gel compositions that have been successfullyintroduced in recent years. It would also be highly desirable to providea method of making enhanced efficacy antiperspirant salts inconcentrated solution—i.e., at salt concentrations greater than 20%.Such a method would be more efficient than current methods, whichgenerally require dilute solutions, thus necessitating removal of largeamounts water to obtain the powdered salts.

SUMMARY OF THE INVENTION

The present invention embraces enhanced efficacy antiperspirantcompositions containing strontium, particularly enhanced efficacyantiperspirant salts containing strontium and an amino acid or a hydroxyacid, methods of making such enhanced efficacy antiperspirant saltcompositions, stabilized aqueous solutions of such enhanced efficacyantiperspirant salt compositions, and topical compositions containingsuch enhanced efficacy antiperspirant salt compositions.

One composition in accordance with the present invention comprises, inpercent by weight, about 5% to about 82% (USP), preferably about 10% toabout 78% (USP), of an enhanced efficacy aluminum or aluminum-zirconiumantiperspirant salt, about 1% to about 85%, preferably about 4% to about75%, water, an amino acid or a hydroxy acid in an amount to provide an(amino or hydroxy) acid:Al+Zr weight ratio of about 2:1 to about 1:20,preferably about 1:1 to about 1:10, and a soluble strontium salt in anamount to provide a Sr:Al+Zr weight ratio of about 1:1 to about 1:28,preferably about 1:2 to about 1:25. Somewhat lower amounts of thestrontium salt may be used if a calcium salt is also included (e.g., inaccordance with the teachings of U.S. Pat. No. 6,042,816, which isincorporated herein by reference). Preferred solid antiperspirant saltcompositions will comprise about 48% to about 82% (USP), preferablyabout 66% to about 78%, of an enhanced efficacy aluminum oraluminum-zirconium antiperspirant salt and about 1% to about 16%,preferably about 4% to about 13%, bound water along with theaforementioned amount of strontium salt and amino acid or hydroxy acid.Preferred aqueous liquid compositions will comprise about 10% to about45% (USP), preferably about 20% to about 42%, antiperspirant salt andabout 20% to about 80%, preferably about 25% to about 75%, water alongwith the aforementioned amount of strontium salt and amino acid orhydroxy acid. The HPLC peak 4 to peak 3 area ratio of the antiperspirantsalt in these compositions does not degrade as quickly or to as low apoint as similar compositions without the strontium salt and amino acidor hydroxy acid.

The present invention also embraces a topical composition comprising adermatologically acceptable carrier vehicle and an antiperspiranteffective amount of a stabilized enhanced antiperspirant saltcomposition as described above. Preferably, the topical antiperspirantcomposition will comprise a dermatologically acceptable carrier vehicle,about 8% to about 22% (USP) of an enhanced efficacy aluminum-zirconiumchlorohydrate-glycine antiperspirant salt having an HPLC peak 4 to peak3 area ratio of at least 0.5 with at least 70% of the aluminum containedin said peaks 3 and 4, wherein the glycine is present in an amount toprovide a glycine:Al+Zr weight ratio of about 2:1 to about 1:20, andabout 0.5% to about 10%, preferably about 1% to about 6%, of a solublestrontium salt. In such a composition the carrier vehicle may beanhydrous and the antiperspirant salt and the strontium salt may besuspended in the carrier vehicle (e.g., a silicone oil). However, it ispreferred that the antiperspirant salt and the strontium salt aresolubilized in the carrier vehicle, particularly when the carriervehicle comprises water and/or a polyhydric alcohol.

One method of the present invention involves stabilizing an aqueoussolution of an enhanced efficacy aluminum or aluminum-zirconiumantiperspirant salt against rapid degradation of the HPLC peak 4 to peak3 area ratio of said salt by adding to said aqueous antiperspirant saltsolution an effective amount of a soluble strontium salt and a watersoluble amino acid or hydroxy acid to form a stabilized aqueous enhancedantiperspirant salt solution. A second disclosed method involvespreparing an enhanced efficacy aluminum or aluminum-zirconiumantiperspirant salt by heating an aqueous solution of an aluminum or analuminum-zirconium antiperspirant salt in the presence of a solublestrontium salt and a water soluble amino acid or hydroxy acid at atemperature and for a time sufficient to convert the salt to an enhancedantiperspirant salt.

A third disclosed method is an improvement in the method of making analuminum hydroxy halide or an aluminum hydroxy nitrate by reactingaluminum with an aqueous solution of aluminum halide or aluminum nitrate(or with aqueous hydrogen halide or nitric acid), wherein theimprovement comprises including a soluble strontium salt and a watersoluble amino acid or hydroxy acid in the reaction mixture. This methodprovides an aqueous solution of an aluminum antiperspirant salt of theformula Al₂(OH)_(6-a)X_(a) wherein X is Cl, Br, I or NO₃ and a is about0.3 to about 5 by reacting aluminum with an aqueous solution of AlX₃ orHX, wherein the amount of aluminum, the amount of AlX₃ or HX, and thetime and temperature of reaction are selected so as to provide saidantiperspirant salt of the formula Al₂(OH)_(6-a)X_(a) at a concentrationof about 5% to about 45% (USP) by weight, and wherein said aqueoussolution of AlX₃ or HX additionally comprises a soluble strontium saltand a water soluble amino acid or hydroxy acid in the reaction mixturein an amount to provide a Sr:Al weight ratio of about 1:1 to about 1:28and an acid:Al weight ratio of about 2:1 to about 1:20.

A fourth method of the present invention involves the preparation of anenhanced aluminum-zirconium antiperspirant salt by the addition of azirconium antiperspirant salt to an aqueous solution of an enhancedaluminum antiperspirant salt prepared by one of the above-describedmethods, wherein the amount of zirconium antiperspirant salt is such asto provide an Al:Zr ratio of about 2:1 to about 10:1.

DETAILED DESCRIPTION OF THE INVENTION

Preferred aluminum salts are those having the general formulaAl₂(OH)_(6-a)X_(a) wherein X is Cl, Br, I or NO₃, and a is about 0.3 toabout 5, preferably about 0.8 to about 2.5, more preferably about 1 toabout 2 (such that the Al to X mole ratio is about 0.9:1 to about2.1:1). These salts generally have some water of hydration associatedwith them, typically on the order of 1 to 6 moles per mole of salt. Mostpreferably, the aluminum salt is aluminum chlorohydrate (i.e., X is Clin the above formula), especially 5/6 basic aluminum chlorohydrate wherea is about 1, such that the aluminum to chlorine mole ratio is about1.9:1 to 2.1:1. Aluminum chlorohydrate is referred to as “ACH” herein.

Preferred aluminum-zirconium salts are mixtures or complexes of theabove-described aluminum salts with zirconium salts of the formulaZrO(OH)_(2-pb)Y_(b) wherein Y is Cl, Br, I, NO₃, or SO₄, b is about 0.8to 2, and p is the valence of Y. The zirconium salts also generally havesome water of hydration associated with them, typically on the order of1 to 7 moles per mole of salt. Preferably the zirconium salt iszirconium hydroxychloride of the formula ZrO(OH)_(2-b)Cl_(b) wherein bis about 0.8 to 2, preferably about 1.0 to about 1.9. Thealuminum-zirconium salts encompassed by the present invention have anAl:Zr mole ratio of about 2 to about 10, and a metal:X+Y ratio of about0.73 to about 2.1, preferably about 0.9 to 1.5. A preferred salt isaluminum-zirconium chlorohydrate (i.e., X and Y are Cl), which has anAl:Zr ratio of about 2 to about 10 and a metal:Cl ratio of about 0.9 toabout 2.1. Thus, the term aluminum-zirconium chlorohydrate is intendedto include the tri-, tetra-, penta- and octa-chlorohydrate forms.Aluminum-zirconium chlorohydrate is referred to as “ACH/ZHC” or as“AZCH” herein.

The aluminum and aluminum-zirconium salts of the present invention areof the enhanced efficacy type. By “enhanced efficacy salt” is meant anantiperspirant salt which, when reconstituted as a 10% aqueous solution(or if already a solution, diluted with water to about 10% saltconcentration in solution), produces an HPLC chromatogram wherein the Alis resolved into at least four distinct peaks (conveniently labeledpeaks 2 (or 1+2), 3, 4 and 5), such as is shown in U.S. Pat. No.5,330,751, which is incorporated herein by reference, wherein at least70%, preferably at least 80%, of the aluminum is contained in peaks 3and 4, and wherein the ratio of the area under peak 4 to the area underpeak 3 is at least 0.5, preferably at least 0.7, and more preferably atleast 0.9 or higher. Most preferred are salts which exhibit an HPLC peak4 to peak 3 area ratio of at least 0.7 when measured within two hours ofpreparation, and which retain a peak 4 to peak 3 area ratio of at least0.5, preferably at least 0.7, when stored as an aqueous solution of atleast 20% salt concentration for one month. Especially preferred aresalts wherein at least 30%, more preferably at least 40%, of thealuminum is contained in peak 4. The aluminum present in peaks 3 and 4should be of the Al^(c) type, not Al^(b), when analyzed by the ferrontest. Enhanced efficacy aluminum chlorohydrate is referred to as “ACH′”herein. Enhanced efficacy aluminum-zirconium chlorohydrate is referredto as “ACH′/ZHC” or as “AZCH′” herein.

The enhanced antiperspirant salts of the present invention have adistinct advantage over previously known enhanced antiperspirant saltsin that they will maintain their enhanced state (i.e., they willmaintain an elevated peak 4 to peak 3 ratio) in aqueous solution (i.e.,solutions containing more than 18% water, typically 20% to 85% water),even at relatively high salt concentrations—for example, at saltconcentrations of 18% to 45% (USP) by weight.

The compositions of the present invention include soluble strontiumsalts. By soluble is meant those strontium salts which are soluble inwater or which dissolve in the aqueous solution of antiperspirant salt(i.e., a solution of the aluminum salt and/or zirconium salt). Strontiumsalts that may be utilized are any of those that do not otherwiseinterfere with the solubility or effectiveness of the antiperspirantsalt. Preferred strontium salts include strontium chloride, strontiumbromide, strontium nitrate, strontium citrate, strontium formate,strontium acetate, strontium gluconate, strontium ascorbate, strontiumlactate, strontium glycinate and mixtures thereof. Strontium carbonate,strontium sulfate and strontium hydroxide may also be used because theywill dissolve in an aqueous solution of the antiperspirant salt. Theamount of strontium salt utilized should be that amount which provides aSr:Al+Zr weight ratio of about 1:1 to about 1:28, preferably about 1:2to about 1:25. Generally, the aqueous antiperspirant solution willcontain about 0.3% to about 3.5% by weight Sr (excluding the anion),preferably about 0.5% to about 3.0% by weight Sr, most preferably about1.0% to about 2.5% by weight Sr, based on the weight of the entirecomposition. These amounts of strontium in the final composition may beobtained by the inclusion of about 0.5% to about 10%, preferably about1% to about 6%, by weight of strontium chloride, nitrate, sulfate,glycinate or similar salts.

The compositions of the present invention also contain a water solubleamino and/or hydroxy acid which is effective in increasing and/orstabilizing the HPLC peak 4:3 area ratio of the antiperspirant salt.Such acids include amino—and/or hydroxy-substituted lower alkanoic acids(including substituted derivatives thereof), preferably where the aminoor hydroxy group is located on the α-carbon (i.e., the same carbon towhich the carboxy group is attached). The lower alkanoic acid willgenerally have 2 to 6, preferably 2 to 4, carbon atoms in the alkanoicacid chain. Typical amino and/or hydroxy substituted lower alkanoicacids include any of the amino acids such as glycine, alanine, valine,leucine, isoleucine, β-alanine, serine, cysteine, β-amino-n-butyricacid, γ-amino-n-butyric acid, etc. and hydroxy acids such as glycolicacid and lactic acid. These amino and/or hydroxy substituted loweralkanoic acids may also contain various substituents which do notadversely affect their activity. The preferred amino and/or hydroxysubstituted lower alkanoic acids are glycine, alanine, and glycolicacid, with glycine being most preferred. The amount of amino acid orhydroxy acid utilized should be that amount which provides an acid:Al+Zrweight ratio of about 2:1 to about 1:20, preferably about 1:1 to about1:10, and most preferably about 1:2 to about 1:7. Generally, the aqueousantiperspirant solution will contain about 1% to about 15% by weightamino acid or hydroxy acid, preferably about 2% to about 10% by weight,based on the weight of the entire composition. The amino and/or hydroxyacid need not be separately added to the composition, but may beincluded as part of the antiperspirant salt complex such as, forexample, Al—Zr-Gly salts (e.g., aluminum-zirconium tetrachlorohydrex-glyor aluminum-zirconium octachlorohydrex-gly). The glycine content of suchsalts may be adjusted to provide the aforementioned ratio. The aminoand/or hydroxy acid may also be added as a salt, particularly thestrontium salt such as, for example, strontium glycinate.

Stabilization of Enhanced Antiperspirant Salt Solutions with Strontiumand Amino or Hydroxy Acid.

One aspect of the present invention involves the preparation ofstabilized aqueous solutions of enhanced efficacy antiperspirant saltsby the inclusion of strontium and an amino acid or hydroxy acid. Thatis, an aqueous solution of an enhanced antiperspirant salt, which wouldordinarily lose 4:3 peak ratio rapidly, particularly at higherconcentrations, may be stabilized by the inclusion of strontium and anamino acid or hydroxy acid in the solution. By “stabilized” is meantthat the peak 4 to peak 3 ratio, while it may degrade somewhat, will notdegrade as quickly or to as low a point as an unstabilized salt (i.e., asalt solution without strontium and amino acid present). That is, thepeak 4 to peak 3 ratio (HPLC area) will remain at 0.5 or higher,preferably at least 0.7, for at least one month at room temperature. Toachieve stabilization the composition will comprise in percent by weight(USP) about 18% to about 45%, preferably about 20% to about 42%,antiperspirant salt, about 20% to about 80%, preferably about 25% toabout 70%, water, an amino acid or a hydroxy acid in an amount toprovide an acid:Al+Zr weight ratio of about 2:1 to about 1:20,preferably about 1:1 to about 1:10, and a soluble strontium salt in anamount to provide a Sr:Al+Zr weight ratio of about 1:1 to about 1:28,preferably about 1:2 to about 1:25. This aspect of the invention may bedemonstrated by Examples 1 and 2 below.

EXAMPLE 1

An aqueous solution containing 20% (USP) enhanced aluminum-zirconiumtetrachlorohydrex-gly (AZCH′-gly; Al:Zr=3.6 (mole ratio); Gly:Al+Zr1:2.5 (wt. ratio)) was prepared by dissolving the powdered salt inwater. The powdered salt had been previously prepared by heating anapproximately 10% aqueous solution of ACH at about 85° C. for about 16to 20 hours, adding ZHC-gly, then spray drying. To this solution wasalso added an amount of strontium chloride hexahydrate to provide theconcentration of Sr and the Sr:Al+Zr weight ratio indicated in theTable. The HPLC peak 4 to peak 3 area ratio five weeks after preparationis also given.

TABLE 1 Stability of 4/3 Ratio of Aqueous 20% Enhanced AZCH′-Gly WithStrontium AZCH′-Gly % (USP) 20% 20% 20% 20% Sr %  0%  0.5%  1.0%  1.5%Sr:Al + Zr (wt. ratio)  0  1:15  1:7.5  1:5 4/3 ratio, t = 5 wks  0.35 0.87  1.20  1.46

As will be seen from the above data, the addition of 0.5% to 1.5%strontium to a 20% aqueous aluminum-zirconium tetrachlorohydrex-glysolution (Gly:Al+Zr=1:2.5) stabilizes the 4:3 peak ratio at a high level(i.e. >0.7), whereas the solution without strontium drops below 0.5.Generally, peak ratio increases as strontium level increases. Similarresults are obtained with other strontium salts such as strontiumnitrate, strontium sulfate and strontium glycinate. Also, mixtures ofstrontium salts and calcium salts can be used. In addition, aqueoussolutions containing higher concentrations of AZCH′-gly salts (e.g., 30%solutions) have stabilized peak 4:3 ratios when strontium salts (ormixtures of strontium and calcium salts) are included.

EXAMPLE 2

Aqueous solutions containing 25% (USP) enhanced aluminum chlorohydrate(ACH′) are prepared by dissolving an appropriate amount of the powderedenhanced salt in water. The powdered salt can be prepared by heating anapproximately 10% aqueous solution of ACH at about 85° C. for about 16to 20 hours, then spray drying. To each of these solutions is added anamount of strontium chloride hexahydrate and glycine (or alanine orglycolic acid) to provide the concentration of Sr and glycine (oralanine or glycolic acid) indicated in Table 2. The Sr:Al weight ratioand the (amino or hydroxy) Acid:Al weight ratio for each solution arealso given in Table 2.

TABLE 2 Stability of 4/3 Ratio of Aqueous 25% ACH′ With Strontium &Glycine or Alanine or Glycolic Acid ACH % (USP) 25% 25% 25% 25% 25% 25%25% Sr %  1.0%  1.5%  2.0%  1.0%  1.0%  1.0%  1.0% Sr:Al (wt. ratio) 1:7.5  1:5  1:3.8  1:7.5  1:7.5  1:7.5  1:7.5 Glycine %  4%  4%  4%Alanine %  4%  6% Glycolic Acid %  4%  6% Acid:Al (wt. ratio)  1:1.9 1:1.9  1:1.9  1:1.9  1:1.3  1:1.9  1:1.3

The HPLC peak 4 to peak 3 area ratio for each solution will remain above0.5 after several days storage. The addition of strontium alone orglycine alone to a 25% aqueous enhanced aluminum chlorohydrate solutiondoes not stabilize the 4:3 peak ratio. Both strontium and glycine mustbe present to stabilize the 4:3 peak ratio at a high level (i.e. >0.5).Generally, peak ratio increases as strontium level increases and asglycine level increases. However, the solution may gel with strontiumlevels greater than 3% and (amino) acid levels greater than 6%. Similarresults are obtained with alternative strontium salts, such as strontiumnitrate and strontium sulfate, and with alternative amino acids, such asleucine, isoleucine, β-alanine, cysteine, valine, serine,β-amino-n-butyric acid and γ-amino-n-butyric acid.

The strontium and glycine need not be added separately to theantiperspirant salt solution, but may be advantageously added togetheras strontium glycinate. As a further example, an aqueous strontiumglycinate slurry (made by heating strontium carbonate with glycine inwater) is added to an aqueous solution of enhanced aluminumchlorohydrate to form a solution containing 25% (USP) ACH′, 1% Sr and 2%glycinate. After one week the salt solution will have an HPLC peak 4:3area ratio greater than 0.5.

Powdered Enhanced Antiperspirant Salts Containing Strontium and Amino orHydroxy Acid with High and Stable HPLC Peak 4:3 Area Ratio.

Powdered enhanced antiperspirant salts with high and stable peak 4:3ratios may be prepared by spray drying the aforedescribed solutions ofsuch salts containing strontium and an amino acid. This will producepowdered salts containing about 48% to about 82%, preferably about 66%to about 78%, antiperspirant salt (preferably aluminum-zirconiumchlorohydrate), an amino acid or a hydroxy acid (preferably glycine oralanine) in an amount to provide an acid:Al+Zr weight ratio of about 1:1to about 1:10 (generally, about 5% to about 18% amino acid by weight ofthe powdered composition), and a soluble strontium salt in an amount toprovide a Sr:Al+Zr weight ratio of about 1:1 to about 1:28, preferablyabout 1:2 to about 1:25 (generally, about 1% to about 10% strontium byweight of the powdered composition). Such powdered salts will alsocontain some water of hydration, typically about 1% to about 16%,preferably about 4% to 13%, by weight.

EXAMPLE 3

An aqueous solution containing 20% (USP) enhanced aluminum-zirconiumtetrachlorohydrex-gly (AZCH′-gly; Al:Zr=3.6 (mole ratio);Gly:Al+Zr=1:2.5 (weight ratio)) is prepared by dissolving an appropriateamount of the powdered enhanced salt in water. The powdered salt can beprepared by heating an approximately 10% aqueous solution of ACH atabout 85° C. for about 16 to 20 hours, adding ZHC-gly, then spraydrying. To three different portions of this solution is also added anamount of strontium chloride hexahydrate to provide solutions containingrespectively 1%, 2% and 3% Sr (Sr:Al+Zr=1:7.5, 1:3.8 and 1:2.5). Thesesolutions are allowed to stand for three weeks and then spray dried toprovide powdered salts having the compositions shown in Table 3. Each ofthese salts will have an HPLC peak 4 to peak 3 area ratio >2.

TABLE 3 Powdered Enhanced AZCH′-Gly Containing Strontium AZCH′-Gly %(USP) ˜64% ˜57% ˜52% Sr %    3.3%    5.6%    7.7% Gly %  ˜9%  ˜8%  ˜7%H₂O %   11.9%   12.6%   11.7%Aging Non-Enhanced Antiperspirant Salt Solutions in the Presence ofStrontium and Amino or Hydroxy Acid to form Enhanced Antiperspirant SaltSolutions.

A further aspect of the present invention involves heat treating (oraging) aqueous solutions of non-enhanced antiperspirant salts in thepresence of a soluble strontium salt and an amino and/or hydroxy acid toform solutions of enhanced antiperspirant salts (i.e., salts with peak4:3>0.5 or peak 4>30%). While conventional heat treating generallyrequires relatively low concentrations of the non-enhancedantiperspirant salt, the present process, which includes a strontiumsalt and an amino and/or hydroxy acid, may be performed with relativelyhigh concentrations of the antiperspirant salt (e.g. 18% to 45% USP),thus avoiding the need to remove large quantities of water associatedwith dilute solutions. The concentrated solution of the enhancedantiperspirant salt may then be used directly in finished formulationswhich utilize an aqueous antiperspirant salt (such as in clear gels oraqueous roll-ons) or it may be spray dried or vacuum dried to a powder.

The conversion of aqueous antiperspirant salt (e.g. aluminumchlorohydrate or aluminum-zirconium chlorohydrate) to aqueous enhancedantiperspirant salt is performed by aging the solution at a temperature(typically about 40° to about 100° C.) and for a time (typically about 2to about 120 hours) sufficient to convert the aluminum salt to enhancedefficacy form (i.e., HPLC peak 4 to peak 3 area ratio greater than 0.5,preferably greater than 0.7). The aqueous aluminum salt concentration isgenerally at about 18% to about 45% (USP), preferably about 20% to about42% (USP), during the heat treatment conversion. The amount of strontiumsalt and the amount of amino and/or hydroxy acid will each be aneffective amount to increase and/or stabilize the HPLC peak 4:3 arearatio of the salt. The amount of amino and/or hydroxy acid (preferablyglycine or alanine) will be an amount to provide an acid:Al+Zr weightratio of about 2:1 to about 1:20, preferably about 1:1 to about 1:10(generally, about 2% to about 9% by weight of the solution), and theamount of soluble strontium salt will be an amount to provide a Sr:Al+Zrweight ratio of about 1:1 to about 1:28, preferably about 1:2 to about1:25 (generally, about 0.3% to about 3% by weight of the solution). Thesolution of enhanced antiperspirant salt produced will have a stabilizedpeak 4 to peak 3 ratio. The conversion to the enhanced salt may beconducted at room temperature (about 25° C.), but this may require up toabout two weeks of aging. The conversion may also be performed morequickly with microwave heating or by heating above 100° C. in a closedcontainer under pressure.

In accordance with the present invention, a non-enhancedaluminum-zirconium salt may be heat treated in the presence of astrontium salt and an amino or hydroxy acid to obtain the enhancedaluminum-zirconium salt. However, it is generally more advantageous toprepare enhanced aluminum-zirconium salts by first heat aging thealuminum salt (e.g., ACH) in the presence of a strontium salt and anamino or hydroxy acid to obtain the enhanced aluminum salt (ACH′) withstabilized 4:3 ratio, then adding an appropriate amount of zirconiumsalt (e.g., ZHC) to obtain the desired Al:Zr ratio (typically between 2and 10).

EXAMPLE 4

A solution (4a) was prepared by adding 58.5 g aluminum chlorohydrateACH, 50% solution (˜41% USP)), 2.16 g AlCl₃.6H₂O, 11.03 g SrCl₂.6H₂O,3.52 g Glycine and 24.78 g water. A similar solution (4b) was alsoprepared except that it contained 5.29 g Glycine and 23.02 g water.Thus, solution 4a contained 3.6% Sr and 3.5% Gly, while solution 4bcontained 3.6% Sr and 5.3% Gly. Each solution (which contained about 25%USP ACH) was heated at 80° C. for 7 hours. Solution 4a had an HPLC peak4 to 3 area ratio of 0.71. Solution 4b had an HPLC peak 4 to 3 arearatio of 1.45. Generally, increasing Sr content and/or increasingglycine content increases the resulting 4:3 ratio obtained with the heataging process. In contrast, without the strontium salt or the aminoacid, a concentrated ACH solution will not convert to enhanced form(i.e., peak 4:3>0.5).

EXAMPLE 5

The enhanced ACH solution (4b) prepared in example 4 was blended with20.67 g aqueous zirconium hydroxychloride (ZHC) to obtain a solution ofenhanced efficacy aluminum-zirconium tetrachlorohydrex-gly (27% USP;peak 4:3=1.43). As an alternative method of producing such a salt, thefollowing materials were combined: 58.5 g aluminum chlorohydrate (ACH,50% solution (˜41% USP)), 2.16 g AlC₃.6H₂O, 11.03 g SrCl₂.6H₂O, 5.29 gGlycine, 23.02 g water and 20.67 g aqueous zirconium hydroxychloride(ZHC). This solution was heat treated at 80° C. for 7 hours. Theresulting enhanced efficacy aluminum-zirconium tetrachlorohydrex-gly hadan HPLC peak 4 to 3 area ratio of 0.68. This suggests that higher peakratios may be obtained by heat aging the aluminum salt first, in thepresence of strontium and amino acid, then adding the zirconium saltafter the conversion.

Reaction of Al with AlX₃ or HX in the Presence of Strontium and Amino orHydroxy Acid.

A further aspect of the present invention involves the reaction ofaluminum (Al) with aluminum halide or aluminum nitrate (AlX ₃),typically AlCl₃, or with hydrogen halide or nitric acid (HX), typicallyHCl, to form the aluminum halohydrate (hydroxyhalide) or aluminumhydroxy nitrate (Al₂(OH)_(6-a)X_(a)), typically aluminum chlorohydrate(ACH). This reaction is well-known and is the method generally utilizedto prepare conventional, non-enhanced 50% (˜41% USP) ACH solutions on acommercial basis. It has been suggested that enhanced aluminumchlorohydrate (ACH′) can be prepared directly by this reaction if thereactants are mixed at a relatively dilute concentration so that thefinal concentration of ACH′ in the solution is below 20%, preferablyabout 10%. In this regard see, for example, U.S. Pat. No. 4,859,446,U.S. Pat. No. 4,944,933, and U.S. Pat. No. 5,356,609. This directsynthesis of ACH′ has little or no advantage over the known heattreatment of dilute ACH to form ACH′ since dilute solutions are stillrequired, making it necessary to remove large quantities of water toobtain the desired product in powder form, the only form in which theproduct is stable. In addition, this direct synthesis suffers from thesignificant disadvantage in that a substantial amount of Al^(b) isproduced, typically about 20% to 60% of the total aluminum. This is incontrast to the 2% to 5% Al^(b) produced in the conventional heattreatment of ACH to form ACH′. This Al^(b), which does not provideenhanced efficacy, also appears in peak 4 along with the enhancedAl^(c)′.

In accordance with the present invention, it was discovered that if thereaction of aluminum with aluminum halide (or hydrogen halide) or withaluminum nitrate (or nitric acid) is performed in the presence ofstrontium and an amino acid (or a hydroxy acid), enhanced aluminumhalohydrate or aluminum hydroxy nitrate is preferentially formed even atrelatively high concentrations (i.e., at concentrations greater than20%). These concentrated solutions have an initial HPLC peak 4 to 3 arearatio greater than 0.5, preferably greater than 0.7, and most preferablygreater than 0.9. In addition, the peak ratio is stabilized in anenhanced state (i.e., the peak ratio remains greater than 0.5) for atleast one month in aqueous solution.

The above-described reaction may be carried out within the followingparameters. The amount of aluminum and aluminum halide (or aluminumnitrate or hydrogen halide or nitric acid) added will be anapproximately stoichiometric amount (although a slight excess ofaluminum may be desired) so as to provide about a 5% to about a 45%(USP) solution, preferably about a 20% to 42% (USP) solution, of theenhanced aluminum halohydrate (or aluminum hydroxy nitrate) desired.Concentrations above 20% are preferred for economic efficiency. Theamount of amino acid (preferably glycine or alanine) or hydroxy acidshould be sufficient to provide an acid:Al weight ratio of about 1:1 toabout 1:10 (i.e., typically about 1% to about 12% by weight of the finalsolution). The amount of strontium salt should be sufficient to providea Sr:Al weight ratio of about 1:1 to about 1:28, preferably about 1:2 toabout 1:25 (i.e., typically about 0.3% to about 3% by weight of thefinal solution). The temperature of the reaction may be from about 50°C. to about 120° C., preferably about 80° to 105° C., and the reactiontime may vary, depending on the reaction temperature, from about 1 to100 hours, preferably about 3 to 12 hours, most preferably about 4 to 6hours. Generally, the reaction will be carried out until the desiredaluminum to halide (or nitrate) ratio is achieved (broadly 0.8 to 2.5,and typically 1.9 to 2.1 for 5/6 ACH′).

EXAMPLE 6

Three aluminum chlorohydrate (ACH) solutions were prepared by reacting,at 100° C. for 5 hours in a flask fitted with a condenser, 16.10 g Alwith 34.98 g AlC₃.6H₂O in 148.92 g water. The second solution alsocontained 24.39 g SrCl₂.6H₂O (with water reduced to 124.57 g) and thethird solution contained 24.39 g SrCl₂.6H₂O and 12.0 g glycine (withwater reduced to 112.57 g). The HPLC peak 4 to peak 3 area ratio for thefirst two solutions was less than 0.1, while that of the third solution,which contained both strontium and glycine, was about 0.55.

Preparation of Enhanced Aluminum-Zirconium Aqueous Solutions fromEnhanced Aluminum Solutions and Powdered Salts Therefrom.

In accordance with the present invention, enhanced Al—Zr antiperspirantsalts may be prepared by adding to an aqueous solution of the enhancedaluminum salt made as described previously (e.g. as described in Ex. 4or Ex. 6), an amount of zirconium salt (e.g., zirconium hydroxychloride)sufficient to provide the desired Al:Zr ratio (typically between 2 and10). In this way aqueous solutions of enhanced Al—Zr salts such asenhanced aluminum-zirconium chlorohydrate may be prepared,advantageously at relatively high concentration (i.e., 18-45% USP).These solutions may also be dried, such as by spray drying or vacuumdrying, to provide the enhanced Al—Zr salts in solid (i.e., powder)form.

EXAMPLE 7

About 50 g of the ACH′-Sr-Gly solution described in Example 6 can bemixed with about 29 g of aqueous zirconium hydroxychloride (ZHC) (16.6%Zr) to provide a concentrated solution of enhanced efficacyaluminum-zirconium tetrachlorohydrex-gly (˜32% USP) with an Al/Zr moleratio of about 3.6 and an HPLC peak 4:3 area ratio >0.5. The solutioncan be vacuum dried to provide the salt in solid powder form.

Topical Compositions Containing Stabilized Enhanced Antiperspirant Saltsof the Present Invention.

Any of the aforedescribed stabilized enhanced antiperspirant salts maybe formulated into topical compositions such as aerosols, pump sprays,roll-ons, lotions, creams, gels, sticks, etc. Such topical compositionswill include the antiperspirant salt, typically in an amount of about 8%to about 22% (USP), a dermatologically acceptable carrier vehicle(including, for example, water, alcohol, polyhydric alcohol, organicoil, silicone oil, etc.), the amino and/or hydroxy acid, and thestrontium salt. In particular, aqueous solutions of these stabilizedantiperspirant salts may be directly utilized in oil-in-water andwater-in-oil emulsions, such as the currently popular clear gelformulations, or in other aqueous based compositions such as aqueousalcoholic based roll-ons. The powdered enhanced salts may be formulatedinto any known type of topical composition which utilizes powderedsalts, including, in particular aerosol, liquid roll-on, cream and solidstick formulations in which the powdered salt is suspended in ananhydrous, dermatologically acceptable carrier, particularly a carriercomprising a silicone.

EXAMPLE 8

A clear antiperspirant gel composition comprising the followingingredients, in which all parts and percentages are by weight, isprepared following the procedure outlined below.

Water 8.37 Al—Zr Tetrachlorohydrex-Gly/Sr¹ 60.63 Propylene Glycol 2.25Ethanol 11.00 Dimethicone (DC-200 10 cst) 1.75 Dimethicone Copolyol(DC-5225C) 9.60 Dimethicone & Trisiloxane (DC 2-1184) 6.15 Fragrance0.25 ¹29% (USP) aqueous solution containing about 2% Sr and 3% GlyThe water phase components (AZCH′-Gly/Sr, propylene glycol, ethanol,water) and the oil phase components are each mixed in separatecontainers and filtered and the refractive index of each is measured.The refractive index of the water phase is adjusted to match therefractive index of the oil phase to within 0.0004 by addition of wateror propylene glycol as required. The water phase is then slowly added tothe oil phase at about 18° C. with sufficient mixing to form a clearemulsion with minimum aeration. This emulsion is then sheared to form aclear gel with a viscosity of about 130,000 to 160,000 cP. This productwill exhibit superior thermal efficacy compared to a conventional cleargel antiperspirant product.

Throughout the specification reference to HPLC analysis means thatchromatograms were obtained as follows: Salt solutions are evaluated foraluminum polymer distribution by HPLC at a concentration of about 10% Alor Al—Zr salt. If the solution to be analyzed is at a higher saltconcentration, it is diluted with sufficient water to bring the saltconcentration to about 10%. A 1.0 μL sample is pumped through a 4.6mm×50 cm column packed with Nucleosil 100-5 (Keystone Scientific Inc.)using a 0.01 M aqueous nitric acid solution as the eluent. The flow rateof the mobile phase was controlled at 0.5 mL/min with a Waters 100 unit.HPLC profiles were recorded and processed with a computerized systemthat included the Millennium 2010 Chromatography Manager software fromthe Millipore/Waters Corp. A Waters 410 differential refractometer wasused as the refractive index detector. The HPLC profiles are read fromleft to right (higher to lower molecular weight). Following thistechnique, peaks 3 and 4 generally appear at retention times of about9.2 to about 10.0 minutes and about 10.5 to about 11.2 minutes,respectively. Naturally, of course, other HPLC techniques which usedifferent column materials, eluents and flow rates can be used providedthat they sufficiently resolve peaks 3 and 4 with an acceptable degreeof precision (i.e., the technique must be capable of resolving the Alinto at least four distinct peaks). Obviously, such other techniques mayplace peaks 3 and 4 at different retention times from those given above.

It should be noted that reference throughout this application to weightpercent of antiperspirant salt is intended to be calculated as anhydrousweight percent in accordance with the U.S.P. method. This calculationexcludes any bound water and glycine. For aluminum chlorohydrate andaluminum-zirconium chlorohydrate, the calculation is as follows:% ACH=% Al[26.98x+17.01(3x−1)+35.45]/26.98x where x=Al/Cl ratio;% AZCH=% Al{26.98y+92.97+17.01[3y+4−(y+1)/z]+35.45(y+1)/z}/26.98y wherey=Al/Zr ratio and z=metal/Cl ratio.For reference purposes, calculation of antiperspirant salt weightpercent in accordance with the U.S.P. method compares to the previouslyused standard industry method as follows: 50% ACH (std.)≅40.8% (USP);50% AZCH (std)≅38.5% USP.

1. A composition comprising, in percent by weight, about 5% to about 82%(USP) of an enhanced efficacy aluminum-zirconium-chlorohydrate-glycineantiperspirant salt having an HPLC peak 4 to peak 3 area ratio of atleast 0.5 with at least 70% of the aluminum contained in said peaks 3and 4, wherein the glycine is present in an amount to provide a glycine:Al+Zr weight ratio of about 2:1 to about 1:20, about 1% to about 85%water, and a soluble strontium salt in an amount to provide a Sr:Al+Zrweight ratio of about 1:1 to about 1:28.
 2. The composition of claim 1comprising about 10% to about 78% (USP) of saidaluminum-zirconium-chlorohydrate-glycine antiperspirant salt and about4% to about 75% water, wherein said glycine:Al+Zr weight ratio is about1:1 to about 1:10 and said Sr:Al+Zr weight ratio is about 1:2 to about1:25.
 3. The composition of claim 2 wherein saidaluminum-zirconium-chlorohydrate-glycine antiperspirant salt has an HPLCpeak 4 to peak 3 area ratio of at least 0.7 with at least 80% of thealuminum contained in said peaks 3 and
 4. 4. The composition of claim 3wherein said strontium salt is selected from the group consisting ofstrontium chloride, strontium bromide, strontium nitrate, strontiumcitrate, strontium formate, strontium acetate, strontium gluconate,strontium ascorbate, strontium lactate, strontium glycinate, strontiumcarbonate, strontium sulfate, strontium hydroxide, and mixtures thereof.5. The composition of claim 1 in the form of an aqueous solutioncomprising about 10% to about 45% (USP) of saidaluminum-zirconium-chlorohydrate-glycine antiperspirant salt and about20% to about 80% water.
 6. The composition of claim 4 in the form of anaqueous solution comprising about 20% to about 42% (USP) of saidaluminum-zirconium-chlorohydrate-glycine antiperspirant salt and about25% to about 75% water.
 7. The composition of claim 1 in the form of asolid powder comprising about 48% to about 82% (USP) of saidaluminum-zirconium-chlorohydrate-glycine antiperspirant salt and about1% to about 16% water.
 8. The composition of claim 4 in the form of asolid powder comprising about 66% to about 78% (USP) of saidaluminum-zirconium-chlorohydrate-glycine antiperspirant salt and about4% to about 13% water.
 9. A method of reducing perspiration from humanskin comprising applying to human skin a perspiration reducing effectiveamount of a composition according to claim 1, 5, 6, 7 or
 8. 10. Atopical antiperspirant composition in the form of an aerosol, pumpspray, roll-on, lotion, cream, gel, or stick comprising a perspirationreducing effective amount of a composition according to claim 1, 6, or8.
 11. A clear antiperspirant gel composition comprising a water-in-oilemulsion wherein the water phase comprises a composition according toclaim 5 or
 6. 12. A topical antiperspirant composition comprising aperspiration reducing effect amount of a composition according to claim7 or 8 suspended in an anhydrous carrier.
 13. A topical antiperspirantcomposition comprising a dermatologically acceptable carrier vehicle,about 8% to about 22% (USP) of an enhanced efficacyaluminum-zirconium-chlorohydrate-glycine antiperspirant salt having anHPLC peak 4 to peak 3 area ratio of at least 0.5 with at least 70% ofthe aluminum contained in said peaks 3 and 4, wherein the glycine ispresent in an amount to provide a glycine: Al+Zr weight ratio of about2:1 to about 1:20, and a soluble strontium salt in an amount to providea Sr:Al+Zr weight ratio of about 1:1 to about 1:28.
 14. The compositionof claim 13 wherein the enhanced efficacyaluminum-zirconium-chlorohydrate-glycine antiperspirant salt has an HPLCpeak 4 to peak 3 area ratio of at least 0.7 with at least 80% of thealuminum contained in said peaks 3 and 4, wherein the glycine: Al+Zrweight ratio is about 1:1 to about 1:10, and wherein the Sr:Al+Zr weightratio is about 1:2 to about 1:25.
 15. The composition of claim 13comprising about 0.5% to about 10% strontium salt.
 16. The compositionof claim 14 comprising about 1% to about 6% strontium salt.
 17. Thecomposition of claim 13 or 14 wherein the strontium salt is selectedfrom the group consisting of strontium chloride, strontium bromide,strontium nitrate, strontium citrate, strontium formate, strontiumacetate, strontium gluconate, strontium ascorbate, strontium lactate,strontium glycinate, strontium carbonate, strontium sulfate, strontiumhydroxide, and mixtures thereof.
 18. The composition of claim 13 or 14wherein the carrier vehicle comprises water and the antiperspirant saltand the strontium salt are dissolved in the water.
 19. The compositionsof claim 13 or 14 wherein the carrier vehicle is anhydrous and theantiperspirant salt and the strontium salt are suspended in the carriervehicle.